Modulation of HTLV-I gene expression by HIV-1 Rev through an alternative RxRE-independent pathway mediated by the RU5 portion of the 5'-LTR.
The 5'-RU5 portion of human T-lymphocyte virus type I (HTLV-I) long terminal repeat (LTR) had been reported to contain cis-acting elements for the controlled viral gene expression by the rex gene product. In this study, the human immunodeficiency virus type I (HIV-1) Rev protein was found to enhance gene expression, acting through the 5'-RU5 portion of HTLV-I, while the Rex-responsive element (RxRE)-mediated activation by Rev was reconfirmed to be negative. This positive action of HIV-1 Rev on HTLV-I gene expression seemed to be distinct from the widely accepted Rex or Rev function to facilitate the nuclear export of RxRE-containing unspliced viral mRNAs, since a trans-dominant, nuclear export-deficient mutant (RevM10) still retained the RU5-mediated effector function. Analyses of the functional aspects of Tat/Rev fusion proteins on the HTLV-I RU5 suggested a specific interaction of Rev and RU5, but lacked evidence for the binding of Rev to the RU5 at the RNA level. These results suggest an answer to the controversy regarding a Rex-like function occasionally observed with HIV-1 Rev and its related proteins. It may also be suggested that particular care should be taken when such a trans-dominant Rev mutant is considered to be used as a genetic therapy against HIV-I infection, in individuals infected with both HIV-I and HTLV-1.
Kubota
S
S
Dorrance H. Hamilton Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Furuta
R A
RA
Hatanaka
M
M
Pomerantz
R J
RJ
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002874:Chromosome Mapping; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000235:genetics*; D016370:Gene Products, rex / Q000235:genetics*; D015752:Genes, env; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D016370:Gene Products, rex; D012333:RNA, Messenger; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus